Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Genome Analysis Center, Yamanashi Central Hospital, Yamanashi, Japan.
Cancer. 2023 Jun 1;129(11):1714-1722. doi: 10.1002/cncr.34717. Epub 2023 Mar 18.
Obtaining sufficient pancreaticobiliary tumor tissue for genomic profiling has limitations. Liquid biopsies using plasma do not provide sufficient sensitivity. Thus, this study aimed to determine the effectiveness of liquid biopsy between bile and plasma for identifying oncogenic and drug-matched mutations.
This study created a panel of 60 significantly mutated genes specific to pancreaticobiliary cancer (PBCA) and used it for genomic analysis of 212 deoxyribonucleic acid (DNA) samples (87 bile supernatant, 87 bile precipitate, and 38 plasma) from 87 patients with PBCA. The quantity of extracted DNA from bile and plasma was compared, as were genomic profiles of 38 pairs of bile and plasma from 38 patients with PBCA. Finally, we investigated 87 bile and 38 plasma for the ability to detect druggable mutations.
The amount of DNA was significantly lower in plasma than in bile (p < .001). Oncogenic mutations were identified in 21 of 38 (55%) patients in bile and nine (24%) in plasma samples (p = .005). Bile was significantly more sensitive than plasma in identifying druggable mutations (p = .032). The authors detected 23 drug-matched mutations in combined bile and plasma, including five ERBB2, four ATM, three BRAF, three BRCA2, three NF1, two PIK3CA, one BRCA1, one IDH1, and one PALB2.
Liquid biopsy using bile may be useful in searching for therapeutic agents, and using the obtained genomic information may improve the prognoses of patients with PBCA.
Genomic profiling of formalin-fixed paraffin-embedded tissues may provide actionable targets for molecular and immuno-oncological treatment. However, most pancreaticobiliary malignancies are unresectable and formalin-fixed paraffin-embedded tissues cannot be obtained. Although comprehensive genomic profiling tests using plasma have been used in recent years, the utility of those using bile is not clear. Our study revealed that bile identified more drug-matched mutations than plasma in advanced pancreaticobiliary cancer patients. Bile may help widen the patient population benefiting from targeted drugs.
获取足够的胰腺胆管肿瘤组织进行基因组分析存在局限性。使用血浆的液体活检提供的敏感性不足。因此，本研究旨在确定胆汁和血浆之间的液体活检在识别致癌和药物匹配突变方面的有效性。
本研究创建了一个针对胰腺胆管癌（PBCA）的 60 个显著突变基因的面板，并对 87 名 PBCA 患者的 212 个脱氧核糖核酸（DNA）样本（87 个胆汁上清液、87 个胆汁沉淀物和 38 个血浆）进行了基因组分析。比较了从胆汁和血浆中提取的 DNA 量，以及 38 名 PBCA 患者的 38 对胆汁和血浆的基因组图谱。最后，我们研究了 87 份胆汁和 38 份血浆检测药物治疗相关突变的能力。
与胆汁相比，血浆中的 DNA 量明显较低（p<.001）。在 38 名患者中，21 名（55%）患者的胆汁样本中发现了致癌突变，9 名（24%）患者的血浆样本中发现了致癌突变（p=.005）。胆汁在识别药物治疗相关突变方面明显比血浆更敏感（p=.032）。作者在联合的胆汁和血浆中检测到 23 种药物匹配的突变，包括 5 种 ERBB2、4 种 ATM、3 种 BRAF、3 种 BRCA2、3 种 NF1、2 种 PIK3CA、1 种 BRCA1、1 种 IDH1 和 1 种 PALB2。
使用胆汁进行液体活检可能有助于寻找治疗药物，利用获得的基因组信息可能会改善 PBCA 患者的预后。
